An attempt to save potential addicts

1. DEXTROPROPOXYPHENE - A DRUG TO BE USED JUDICIOUSLY
Dr.Anil Batta
Associate Professor
Medical Biochemistry
Baba Farid University of Health Sciences, Faridkot
Abstract
Dextroprorpoxyphene is an analgesic in the opioids category. It is intended to treat mild pain and has, in
addition, anti-tussive and local anesthetic effects. But analgesic, opioid withdrawal, RLS being major uses along
with, anitussive, antidepressive, muscle cramps activity adverse overdose side effects are cardiac arrhythmias.
Dextroprorpoxyphene is a weak opioid known to cause dependency among recreational users. It is ineffective
for some individuals with the "poor metabolizer" genotype of the liver cytochromeP450 and enzyme CYP2D6.
It does not have much effect on mental cravings; however it can be effective in alleviating physical withdrawal
effects of opioids, such as muscle cramps. It is commonly used to ease the withdrawal symptoms in people
addicted to opioids. Propoxyphene and its metabolite non-Propoxyphene have local anesthetic effects at
concentrations about 10 times those necessary for opioids effects. It relieves the symptoms of restless legs
syndrome (RLS). It also acts as a potent, noncompetitive neuronal receptor agonist as well as weak serotonine
reuptake inhibitor. It has various side effects like Constipation, Itching, Drowsiness, Sore throat, Impaired
alertness, Confusion, Serious or fatal heart rhythms. Owing to its positive causes, a Study was carried out during
my stay at civil hospital at Lehragaga suburb in Sangrur district of Punjab, adverse and verse effects. Aim of the
study was to have a judicious view to prescribe and use the drug for various disorders. Aim of the study was to
compare the clinical findings in the patients taking Dextroprorpoxyphene and the patients taking routine drugs
like non-opioid analgesics, depressed patients taking antidepressants like tricyclics antidepressants, patients of
bronchitis taking antitussives without opioids like codine,athletes with cramps taking non-opioid anti-
inflammatory and analgesics. It was ensured that they are taking drugs having no relevance, mode of action and
side effects similar to opioids.60 patients taking Dextroprorpoxyphene for therapeutic purposes suffering from
various illness were selected for study .
Key words: -- opioid, restless legs syndrome, ant arrhythmic, depression
Introduction
Dextroprorpoxyphene belongs to a group of medicines called opioids. Opioids mimic the
effects of naturally occurring pain reducing chemicals (endorphins). They combine with the
opioid receptors in the brain and block the transmission of pain signals. Therefore, even
though the cause of the pain may remain, less pain is actually felt. An opioid is a chemical
that works by binding to opioid receptors which are principally found in the central nervous
system and the gastrointestinal tract. These receptors are responsible for both verse and
adverse effects. Analgesic effect is due to decreased perception of pain as well as by
increased tolerance. Dextroprorpoxyphene acts as a mu-receptor agonist. Excessive opioid
receptor stimulation is responsible for the CNS and respirarory
depression, and gastrointestinal effects seen in Propoxyphene poisoning. It may also account
for mood elevating effects. In addition, Norpropoxyphene is a more potent local anesthetic
than propoxyphene, and they are both more potent than lidocaine. Local anesthetic activity
appears to be responsible for the arrhythmias and cardiovascular depression seen in
propoxyphene poisoning. Both propoxyphene and norpropoxyphene are potent blockers of
cardiac membrane sodium channels . As a result, propoxyphene and norpropoxyphene
appear to have the characteristics of a Vaughn-wiliams Class Ic antiarrhythmic.
These direct cardiac effects include decreased heart rate (i.e. cardiovascular depression ),
decreased contractility, and decreased electrical conductivity (i.e., increased PR, AH, HV,
and QRS intervals). These effects appear to be due to their local anesthetic activity and are
not reversed by naloxone. Widening of the QRS complex appears to be a result of a
quinidine-like effect of propoxyphene, and sodium bicarbonate therapy appears to have a
positive direct effect on the QRS dysrhythmia. Seizures may result from either opioid or local
Dr. Anil Batta., Int. J. Chem. Res., 2011v01(5), 34-38 ISSN: 2249-0329
IJCSR |SEP - OCT 2011
Available online@www.ijcsr.com
34

2. anesthetic effects. Pulmonary edema may result from direct Pulmonary
toxicity,neurogenic/anoxic effects, or cardiovascular depression.
Napsylate also gives lower peak blood level. Because of different molecular mass, a dose of
100 mg of propoxyphene napsylate is required to supply an amount of propoxyphene
equivalent to that present in 65 mg propoxyphene hydrochloride.Detectable levels of
propoxyphene/dextropropoxyphene may stay in a person's system for up to nine days after
last dose and can be tested for specifically in non-standard urinalysis but may remain in the
body longer in tiny amounts. Propoxyphene will not show up on standard opiate/opioid tests
because it is not chemically related to opiates part of the OPI or OPI 2000 panels, which
detect morphine and related compounds. It is most closely related to methadone.
Dextropropoxyphene is subject to some controversy: while many doctors prescribe it for a
wide range of mildly to moderately painful symptoms as well as for treatment of diarrhea,
many others refuse to prescribe it, citing limited effectiveness. In addition, the therapeutic
index of dextroproxyphene is relatively small.
Caution should be used when administering dextropropoxyphene, particularly with children
and the elderly and with patients who may be pregnant or breast feeding other reported
problems include kidney, liver or respiratory disorders, and prolonged use. Attention should
be paid to concomitant use with tranquilizers, antidepressants or excess alcohol. Opioids
should not be taken with MAOI anti-depressants or for two weeks after they have been
stopped.When taken together with nicoumalone or warfarin the anticoagulant effect of these
medicines may be increased.Dextropropoxyphene may enhance the effect of carbamazepine
an antiepileptic.Darvon, a dextropropoxyphene had been on the market for 25 years, came
under heavy fire in 1978 by consumer groups that said it was associated with suicidal
tendency. It was discussed at the time that people who abuse alcohol and other substances
and take combination dextropoxyphene/acetaminophen (paracetamol) may need to take many
combination tablets to reach euphoria. This is because the amount of dextropropoxyphene per
tablet is relatively low (30–40 mg). The ingested paracetamol - the other component - may
then reach liver toxic levels. In the case of alcoholics, who often already have damaged
livers, even a relatively small overdose with paracetamol may produce hepatotoxicity. The
toxicity of the combination of overdosed dextroproxyphene with its CNS/respiratory
depression and paracetamol induced liver damage can be a recipe for disaster or death. In
Britain co-proxamol is only available on a named patient basis, for long term chronic pain
and only to those who have already been prescribed this medicine. The co-proxamol
preparations available in the UK contained a sub-therapeutic dose of paracetamol, 325 mg per
tablet. Patients were warned not to take more than eight tablets in one day, a total dose of
2600 mg paracetamol per day. This is in comparison to the 4000 mg daily limit on
paracetamol alone, a significantly higher dose. Despite this reduced level, patients were still
at a high risk of overdose: coproxamol was second only to tricyclic antidepressants as the
most common prescription drugs used in overdose. Following the reduction in prescribing in
2005–2007, prior to its complete withdrawal, the number of deaths associated with the drug
dropped significantly. Additionally, patients have not substituted other drugs as a method of
overdose.Propoxyphene should be used with extreme caution, if at all, in patients who have a
history of substance/drug/alcohol abuse, depression with suicidal tendency, or who already
take medications that cause drowsiness (e.g., antidepressants, muscle relaxants, pain
relievers, sedatives, tranquilizers). Fatalities have occurred in such patients when
propoxyphene was misused.
Dr. Anil Batta., Int. J. Chem. Res., 2011v01(5), 34-38 ISSN: 2249-0329
IJCSR |SEP - OCT 2011
Available online@www.ijcsr.com
35

3. Material and Methods
As already explained it is a clinical study for which no investigation was required. The
patients of different clinical diagnosis were selected. But following deterrents were
mandatory:--
1) Patients of age group of 20 to 55 years were selected for the study.
2) Only clinical diagnosis was the criteria for diagnosis.
3) No sex difference was followed.
For study group 60 patients were selected and they were divided into three groups as
explained below
Grouping No. of
patients
Diagnosis Dose of
dextropropoxyphene
Traditional drug
Group—1 21 Moderate to
severe pain
(Muscle
Cramps)
65 mg. 6 hourly. Ibuprofen+Paracetamol
Group---2 18 Depression 65 mg. 8 hourly. Tricyclic
Antidepressents
Group---3 21 Chronic
patients
65 mg. 8 hourly. Analgesic with
antiiflammatory
Sixty patients were divided into 3 groups. The only criteria for ruling out was the intake of
any opioid either as prescription or as a chronic user as an addict. It was ensured that they
always use traditional drug if at all required by themselves or diagnosed by the doctor at least
for the last 6 months. It was also ensured that they were not exposed to any opioid for the last
6 months willingly or as a part of prescription. Whenever required only traditional drugs have
been used. Their prescription for any disease was verified and attendants were taken into
confidence to rule out any behavioral problem.Group-1, 21 patients were selected who had
moderate to severe pain for muscle cramps due to any reason. These patients had always
taken oral rehydration therapy and had irregularly taken traditional drugs only whatever is the
severity of pain as Ibuprofen or combination of ibuprofen with any other drug like
paracetamol or acetylsalicylic and never crossed that limit.
Group—2 patients comprised 18 patients who have been taking tricyclic antidepressant for
mild to moderate depression taking tricyclic antidepressants but never crossed prescribed
limits or taken any other treatment.
Dr. Anil Batta., Int. J. Chem. Res., 2011v01(5), 34-38 ISSN: 2249-0329
IJCSR |SEP - OCT 2011
Available online@www.ijcsr.com
36

4. Group—3 patients comprised 21 patients of any chronic anti-inflammatory disease who were
taking traditional analgesics with anti-inflammatory drugs and never gone beyond that limit
of drugs.
Keeping in view the paucity of resources we could never went for detection of drug or its
metabolite for blood/serum or urine analysis or counterchecking. All these sixty patients were
prescribed dextropropoxyphene within clinical prescription limit as per depicted in table-1 for
three days only because we never wanted to create any other problems for the patients. They
were asked to continue the traditional treatment.
Results
These patients reported to the OPD after three days. The results were heartening. Patients
came to the OPD with an immaculate praise for the centre and more for me. They narrated
that this was the best treatment they ever had. They were having no pain, depression or
cramps. Out of all groups group-2 patients gave unprecedented response.
Discussion
All sixty patients were reexamined for any side effects or any social repercussions from
family members or friends. All were jubilant and were cursing why they didn’t consult me
before. Our aim was over and we successfully tapered off dextropropoxyphene within four
weeks. All this was due to analgesic, muscle relaxant, increased tolerance of pain, restless
legs syndrome (RLS). Pregnancy and Breastfeeding mothers
should not use it during this period. However, other medicines may be safely used in
pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the
unborn baby. Always inform doctor if lady is pregnant or planning a pregnancy, before using
this medicine.
• This medicine should be used with caution during pregnancy, and only if the expected
benefit to the mother is greater than any possible risk to the fetus. The medicine passes into
the breast milk, but at normal doses it is unlikely to harm the baby. This medication may
cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.
Side effects
Medicines and their possible side effects can affect individual people in different ways. The
following are some of the side effects that are known to be associated with this medicine.
Because a side effect is stated here, it does not mean that all people using this medicine will
experience that or any side effect.
• Headache
• Changes in mood
• Addiction to the medicine (dependence)
• Skin rashes
• False perceptions of things that are not really there (hallucinations)
• Dizziness
• Constipation
• Drowsiness
Conclusion
For all practical purposes we concluded that dextropropoxyphene should always be given in
measured dosage to the genuine patients only. Results of group-2 may be more enthusiastic
due to increased level of serotonine in brain and CNS effects. All the patients of Group-1 and
Group-3 felt much less pain due to increased tolerance level analgesic effect, restless legs
syndrome (RLS). So this is concluded that that this drug can act wonders if judiciously used.
Dr. Anil Batta., Int. J. Chem. Res., 2011v01(5), 34-38 ISSN: 2249-0329
IJCSR |SEP - OCT 2011
Available online@www.ijcsr.com
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5. Misuse can bring disaster for the mankind and society and it has all the potential for
becoming an abused drug. Since the last version of this review no new relevant studies have
been identified. The combination of dextropropoxyphene 65 mg with paracetamol 650 mg
shows similar efficacy to tramadol 100 mg for single dose. This conclusion is not robust.
Adverse effects of both combinations were similar. Avoid concurrent use with alcohol or
paracetamol-containing products
Prescribers are reminded that concurrent use of alcohol or other paracetamol-containing
products is contraindicated. Dextropropoxyphene-paracetamol combination products should
not be prescribed for patients who are suicidal or prone to medicine dependence, and should
be prescribed with caution for those patients taking anxiolytics or antidepressants
• Dextropropoxyphene is a painkiller that is used to treat short- and long-term (chronic)
pain. It is a weak opioid (opioids are medicines related to morphine) that relieves pain by
acting on receptors in the brain and spinal cord. It has been available as a prescription,
•
®
. Fatalities have occurred following intentional and accidental overdose, even with low
numbers of tablets, and when normal doses have been taken concurrently with alcohol or
other CNS depressants. The combination of paracetamol and dextropropoxyphene carries an
overdose risk of rapid-onset respiratory arrest and cardiac arrhythmias due to the
dextropropoxyphene component, as well as latent onset of paracetamol-induced hepatic
necrosis
• When taken together with other drugs that have a sedative effect on the central nervous
system, for example, alcohol, sleeping drugs, antidepressant drugs and antihistamines,
drowsiness is likely to be increased.
• Propoxyphene was initially introduced as Propoxyphene hydrochloride. Shortly before
the patent on Propoxyphene expired, Propoxyphene napsylate form was introduced to the
market. Napsylate salt is claimed to be less prone to abuse, because it is almost insoluble in
water and therefore cannot be used for injection. Napsylate also gives lower peak blood level.
Because of different molecular mass, a dose of 100 mg of propoxyphene napsylate is required
to supply an amount of Propoxyphene equivalent to that present in 65 mg Propoxyphene
hydrochloride
References
1.Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom. Co-
proxamol overdose 19 May 2005 (accessed 26 Sept 2006).
2.Reith D, Fountain J, Tilyard M. Opioid poisoning deaths in New Zealand (2001-
2002). NZMJ 2005;118(1209):1-8. (accessed 10 Oct 2006).
3.Pharmacy Retailing (NZ) Ltd. Capadex (dextropropoxyphene hydrochloride 32.5mg and
paracetamol 325mg) capsules data sheet. 22 March 2006.
4.PSM Healthcare Ltd. Paradex (dextropropoxyphene napsylate 50mg and paracetamol
325mg) tablets data sheet. 6 April 2006.
Dr. Anil Batta., Int. J. Chem. Res., 2011v01(5), 34-38 ISSN: 2249-0329
IJCSR |SEP - OCT 2011
Available online@www.ijcsr.com
38